PCDH1

Chr 5

protocadherin 1

Also known as: PC42, PCDH42

NCBI Gene: 5097ENSG00000156453UniProt: Q08174

This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene. [provided by RefSeq, Jul 2008]

0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PCDH1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.24LOEUF
pLI 0.998
Z-score 4.75
OE 0.09 (0.04–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.08Z-score
OE missense 0.68 (0.63–0.73)
504 obs / 739.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.04–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.63–0.73)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 3 / 32.0Missense obs/exp: 504 / 739.7Syn Z: -0.12

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PCDH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
PROTOCADHERIN 1; PCDH1
MIM #603626 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PCDH1 promotes progression of pancreatic ductal adenocarcinoma via activation of NF-κB signalling by interacting with KPNB1.
Ye Z et al.·Cell Death Dis
2022
The PCDH1 gene and asthma in early childhood.
Mortensen LJ et al.·Eur Respir J
2014
Reactive astrocytes promote tumor progression by up-regulating tumor protocadherin 1 expression in lung cancer brain metastasis.
Tang M et al.·Biochem Biophys Res Commun
2024
Protocadherin-1 polymorphisms are associated with eczema in two Dutch birth cohorts.
Koning H et al.·Pediatr Allergy Immunol
2012Cohort
An extensive study of the mechanism of prostate cancer metastasis.
Wang Y et al.·Neoplasma
2018Functional
The prognostic value of MEK pathway-associated estrogen receptor signaling activity for female cancers.
Ng CW et al.·Br J Cancer
2024
Epigenetic regulation of triple negative breast cancer (TNBC) by TGF-β signaling.
Vishnubalaji R et al.·Sci Rep
2021
The involvement of Th17 inflammation and miR-363-3p in airway epithelial barrier dysfunction.
Lässer C et al.·Respir Res
2026
Novel candidate genes in esophageal atresia/tracheoesophageal fistula identified by exome sequencing.
Wang J et al.·Eur J Hum Genet
2021
[Study on expression of PTEN gene and its pseudogene PTENP1 in acute leukemia and correlation between them].
Wang CC et al.·Zhonghua Xue Ye Xue Za Zhi
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools